Action Points

Current statin use is not associated with an increased risk of developing SLE among patients aged ≥40 years, based on a large (>1 million patients) observational study from a British primary care database.

Note that this study contradicts previous studies suggesting that statins may increase the development of systemic lupus, and there are no randomized trials to settle the controversy.

Data from a large British registry indicated no increased risk of developing systemic lupus erythematosus (SLE) in current statin users ages 40 and older. In fact, there were hints of a possible protective effect.

The matched cohort study selected patients in the U.K.'s Clinical Practice Research Datalink, an ongoing primary care database, who had received one statin prescription during 1995-2009 and matched them by age, sex, practice, and date of first prescription to non-users.

Of the 1,039,694 sample, 519,847 were statin recipients. The mean age in both cohorts was about 63 years and about 48% in both groups were female.

Not surprisingly, statin users were more likely to be previous smokers and to have been diagnosed with cardiovascular disease, hyperlipidemia, hypertension, and diabetes, as well as to have taken aspirin, antihypertensives, antidiabetic agents, and proton pump inhibitors.

The overall incidence rate of SLE in the study population was 0.7 cases per 10,000 person-years. Current statin users ≥40 years of age had a risk of developing SLE moderately but non-significantly lower than in non-users, for an adjusted hazard ratio of 0.75 (95% CI 0.53-1.07).

"This study evaluated a very large number of total records – over 1,000,000 patients ... Therefore, this study contradicts any previous studies suggesting that statins may increase the development of systemic lupus," said Donald E. Thomas, Jr., MD, of the Uniformed Services University of the Health Sciences in Bethesda, Md., in comments to MedPage Today.

"If I were to recommend that one of my patients with SLE take a statin, and if that patient were to raise their concern because they had read an article on the internet stating that statins may potentially cause lupus, I would point out this much stronger article showing no increase in the development of lupus in a large patient population who took a statin," said Thomas, who was not involved with the study.

The study observed that current statin users who continued therapy for >1 year had a significant 38% decrease in SLE risk (adjusted HR 0.62, 95% CI 0.42-0.93).

Thomas cautioned, however, that the researchers' main definition of SLE -- a diagnosis listed in primary care records -- was nonspecific and when a more specific definition was applied, the 38% decline in >1-year users was canceled.

Furthermore, the study's reliance on prescription data rather than drug adherence could lead to an overestimation of statin use in this population, said Thomas, asserting that only randomized trials could settle the matter.

Beyond their lipid-lowering action, statins are thought to have both anti- and proinflammmtory immunomodulating effects. Earlier research has suggested they may facilitate the development of autoimmunity, and some studies analyzing adverse drug reactions have suggested that statins may specifically trigger a lupus-like syndrome.

In a 2011 study, for example, the Dutch investigators had found statin use to be more frequent in patients with lupus-like syndrome than in patients with other adverse drug events, findings consistent with those of a French pharmacovigilance database analysis.

"Statins may not cause autoimmunity by themselves, but they may promote a pre-existing autoimmune-prone condition to progress toward a clinical[ly] manifest disease," Klungel and associates wrote.

As to mechanisms, the authors proposed that statins may protect against SLE by skewing T cell differentiation toward regulatory T cells and away from proinflammatory T helper 17 cells. But they may also promote a shift in the balance of T helper 1 and 2 cells or lead to unstable peripheral regulatory T cells, thereby fostering autoimmunity.

Notably, the authors conceded that their study population was not reflective of typical SLE patients -- young women -- and thus may not be generalizable.

In addition, the investigators had no information on dietary intake, physical activity, and race or ethnicity in a cohort drawn from a largely Caucasian population. Race may prove relevant in other studies as SLE occurs more frequently in blacks. Furthermore, data on potential confounders such as lipid, blood pressure and glucose levels, and inflammatory markers were limited.

This work was supported by the National Institute for Public Health and the Environment. The authors declared financial support fromthe National Institute for Public Health and the Environment. Senior author Klungel received funding from the private-public Top Institute Pharma, The Netherlands, and the Innovative Medicines Initiative Joint Undertaking, which includes financial support from the European Union's Seventh Framework Program, and companies in the European Federation of Pharmaceutical Industries and Associations.

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.